Water soluble haloanilide calcium-release calcium channel inhibitory compounds and methods to control bone erosion and inflammation associated with arthritides

Abstract

A compound that is selected from the group consisting of 3-(3,4-dichloroanilino)-3-oxopropanoic acid (hereinafter “DCOPA”); N-methyl-DCOPA; N,2-dimethyl-DCOPA; 2-methyl-DCOPA; isobutyl-DCOPA; N-methyl-isobutyl DCOPA; 3-(3,4-bibromoanilino)-3-oxopropanoic acid; and analogs of DCOPA; and analogs of 3-(3,4-bibromoanilino)-3-oxopropanoic acid; and pharmaceutically acceptable salts of these compounds, are disclosed. A method of controlling bone erosion in a patient comprising administering to the patient a therapeutically effective amount of at least one of these compounds, or a pharmaceutically acceptable salt of at least one of these compounds, is provided. A method of reducing inflammation in a patient having an inflammatory condition comprising administering to the patient a therapeutically effective amount of at least one of these compounds, or a pharmaceutically acceptable salt of at least one of these compounds is provided.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This utility patent application claims the benefit of U.S. Provisional Patent Application Ser. No. 62 / 307,728, filed on Mar. 14, 2016. The entire contents of U.S. Provisional Patent Application Ser. No. 62 / 307,728 is incorporated by reference into this utility patent application as if fully written herein.BACKGROUND OF THE INVENTION[0002]Field of the Invention[0003]We have shown previously that analogs of DCPA retain the ability to block calcium-release activate calcium (CRAC) channels as the parent compound DCPA (N-(3,4-dichlorophenyl)propanamide) but by design, are not metabolized to more toxic N—OH or 6-OH metabolites of the parent compound. The difficulty with these compounds is that they are not water soluble and this makes development of a drug delivery modality more challenging. The compounds of this patent application have been modified at the amide chain with a hydrogen bond acceptor or ionizable functional group like an acid. A ...

AI Technical Summary

Benefits of technology

The present invention provides a compound called 3,4-dichloro-N-methylaniline, which has the formula 3,4-DCOPA. This compound has been found to have therapeutic effects in controlling bone erosion and reducing inflammation in patients. The invention also provides pharmaceutically acceptable salts of DCOPA and analogs of the compound. The technical effect of this invention is to provide a new compound that can be used to treat bone-related diseases such as osteoporotic bone erosion and rheumatoid arthritis.

Problems solved by technology

DCPA and its analogs, e.g., N-methyl-DCPA, are very hydrophobic which presents challenges to developing a drug using these compounds.

However, none of these drugs are effective at preventing bone erosion that occurs in a significant percentage of arthritis patients

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